Background/Objectives: Hyperuricemia (HUA) is the second most common metabolic disease in China (24.5% in males, 3.6% in females), which can induce multiple complications such as gout and diabetes. Existing urate-lowering drugs have significant hepatorenal toxicity, necessitating safe lifestyle interventions. Electrolyzed alkaline water (EAW) as daily drinking water has shown preliminary effectiveness, but it lacks randomized controlled evidence and mechanistic studies at the microbiome–metabolome interface. Methods: We conducted a 12-week randomized controlled trial in 40 adults aged 18–65 years with elevated serum uric acid (SUA). Participants consumed either 1.5 L/day of EAW (pH 8.5–9.5) or purified water (pH 7.0). Clinical indicators, quality of life (SF-36), gut microbiota, and gut metabolomics were comprehensively assessed to evaluate intervention efficacy and explore potential mechanisms. Results: After 12 weeks, the EAW group exhibited a larger reduction in serum uric acid than the control group, along with improvements in selected physical health-related quality-of-life measures. Modest differences in gut microbial composition were observed between groups. Metabolomic analyses identified group-level differences in metabolites enriched in pathways related to purine metabolism and other urate-associated metabolic processes. Conclusions: This pilot randomized controlled trial suggests that consumption of EAW is associated with a modest reduction in serum uric acid. Exploratory multi-omics analyses indicate concurrent changes in gut microbiota and metabolic profiles. These findings support further investigation of electrolyzed alkaline water as a potential adjunctive, non-pharmacological option for hyperuricemia in larger and longer-term studies. Ethics: This trial was registered with the Chinese Clinical Trial Registry under the identifier ChiCTR2500100190. Ethical approval for the present study was granted by the Nankai University Institutional Review Board (NKUIRB2025001, 23 January 2025).

2′-Fucosyllactose (2′-FL) represents a significant constituent within human milk oligosaccharides, and its benefits for intestinal health and neurodevelopment in infants and young children have been widely recognized. However, the mechanism by which 2′-FL influences early-life behavioral development through the gut–brain axis remains incompletely understood. In this study, we investigated the effects of neonatal 2′-FL supplementation on behavioral development in Sprague-Dawley (SD) rats and explored its potential microbiota-metabolite regulatory mechanisms. After 4 consecutive weeks of oral gavage beginning on postnatal day 2, rats receiving 2′-FL showed significantly increased average movement speed and central-area exploration time in the open field test. From a systemic perspective, 2′-FL lowered blood diamine oxidase (DAO) and D-lactic acid (D-LA) concentrations while elevating colonic mRNA levels of tight junction protein-related genes, consequently enhancing intestinal barrier stability. In addition, 16S rRNA sequencing showed that 2′-FL reshaped the gut microbiota structure and significantly enriched Lactobacillus, Bacteroides, and short-chain fatty acid (SCFA)-associated taxa represented by Lachnospiraceae_NK4A136_group. Untargeted metabolomics revealed that 2′-FL induced systemic metabolic remodeling, characterized by upregulation of the bioactive metabolites dehydroepiandrosterone sulfate (DHEA-S) and deoxycholic acid (DCA), and downregulation of the glucocorticoid-related corticosterone. Western blot validation further showed higher hippocampal protein expression of postsynaptic density protein 95 (PSD95), brain-derived neurotrophic factor (BDNF), and synaptophysin in the 2′-FL group, supporting enhanced synaptic plasticity-related signaling. In summary, neonatal 2′-FL intervention enhanced exploratory behavior and was accompanied by increased hippocampal synaptic plasticity-related protein expression in rats, potentially through coordinated regulation of gut microbiota composition and systemic metabolism.